Abstract

Cystic fibrosis is the most common fatal genetic disorder in the Northern European population; however early diagnosis and treatment can lead to increased quality and length of life for affected individuals and therefore its diagnosis is of great public health significance. Cystic fibrosis is a monogenic recessive disorder caused by mutation in the CFTR gene. Current screening methods include newborn screening tests and invasive prenatal diagnostic tests. Newborn enzymatic screening tests are prone to false positive results, leading to unwarranted stress and anxiety for new parents. Invasive prenatal testing is available, but these invasive procedures carry some risks including miscarriage which also causes anxiety and stress for parents. Non-invasive prenatal testing for fetal aneuploidy using cell-free fetal DNA derived from maternal plasma is now part of the regular clinical offering for women in their first trimester of pregnancy. No commercial non-invasive prenatal test for monogenic disease is currently available. The goal of this study is to develop a non-invasive prenatal test for the detection of the mutation status of the fetus. Proposed here are methods to haplotype the parents in the CFTR region and to genotype the plasma to establish the mutation status of the fetus. In comparison to newborn screening or invasive diagnostic tests, a non-invasive prenatal test for cystic fibrosis would have little to no risk and also provide parents more time to identify clinical and psychosocial resources to facilitate their family’s needs and decision-making processes.